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Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

World Journal of Gastroenterology 2024年第7期30卷 663-672页

作者： xiao-Fei Cheng Feng zhao Dong Chen Fan-Long Liu Department of Colorectal Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Radiation Oncology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment

关键词： Neoadjuvant therapy Colorectal cancer liver metastasis Multidisciplinary teams Chemotherapeutic regimens Resectability criteria

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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3β Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia zhao Yan-na YU xiao-ling YIN Li-ming Department of Hematology Tongde Hospital of Zhejiang Province Institute of Hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)

Objective: To investigate the role of ginsenoside Rd（GRd） in acute myeloid leukemia（AML） cell differentiation. Methods: AML cells were treated with GRd（25, 50, 100 and 200 μg/mL）, retinoic acid（RA, 0.1g/L） and PD98059（20 mg/mL） for 72 h, cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays, and cell cycle was detected by flow cytometry. Cell morphology and differentiation were observed by Wright-Giemsa staining, peroxidase chemical staining and cellular immunochemistry assay, respectively. The protein expression levels of GATA binding protein 1（GATA-1）, purine rich Box-1（PU.1）, phosphorylated-extracellular signal-related kinase（p-ERK）, ERK, phosphorylated-glycogen synthase kinase-3β（p-GSK3β）, GSK3β and signal transducer and activator of transcription 1（STAT1） were detected by Western blot. Thirty-six mice were randomly divided into 3 groups using a random number table: model control group（non-treated）, GRd group [treated with 200 mg/（kg·d） GRd] and homoharringtonine（HTT） group [treated with 1 mg/（kg·d） HTT]. A tumor-bearing nude mouse model was established, and tumor weight and volume were recorded. Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining. WT1 and GATA-1 expressions were detected by immunohistochemical staining. Results: The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1cell arrest（P<0.05）. GRd treatment induced leukemia cell differentiation, showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation（P<0.05）. GRd treatment elicited upregulation of p-ERK, p-GSK-3β and STAT1 expressions in cells, and reversed the effects of PD98059 on inhibiting the expressions of peroxidase, GATA-1 and PU.1（P<0.05）. After GRd treatment, tumor weight and volume of mice were decreased, and tumor cells underwent massive apoptosis and necrosis（P<0.05）. WT1 level was decreased, and GATA-1 level was significantly increased in subcutaneous tumor

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution

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Molecular Plant 2024年第1期17卷 158-177页

作者： Peng Li Meng-xiao Yan Pan Liu Dan-Jie yang Ze-Kun He Yun Gao Yan Jiang Yu Kong Xin Zhong Sheng Wu Jun yang Hong-Xia Wang Yan-Bo Huang Le Wang xiao-Ya Chen Yong-Hong Hu Qing zhao Ping Xu shanghai Key Laboratory of Plant Functional Genomics and Resources Shanghai Chenshan Botanical GardenShanghai Chenshan Plant Science Research CenterChineseAcademy of SciencesShanghaiChina College of Life Sciences Shanghai Normal UniversityShanghai 200234China State Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghaiChina University of the Chinese Academy of Sciences Beijing 100049China The Research Center of Chiral Drugs Innovation Research Institute of Traditional Chinese MedicineShanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China College of Chemistry and Chemical Engineering Shanghai University of Engineering ScienceShanghai 201620China

The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich composition.Leonurine,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating strokes.However,the biosynthetic pathway of leonurine remains largely unexplored.Here,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine production.By integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this pathway.Further analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L.japonicus,which contributed to the accumulation of leonurine specifically in L.japonicus.Collectively,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

关键词： Lamiaceae Leonurus japonicus Leonurus sibiricus genome sequence alkaloids leonurine gene cluster biosynthetic pathway evolution

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Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients

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World Journal of Clinical Cases 2024年第14期12卷 2308-2315页

作者： Jin-Li Gao Jue Shen Li-Ping yang Li Liu Kai zhao xiao-Rong Pan Lei Li Ji-Ji Xu Department of Prevention and Health Care Community Health Service Center of Miaohang TownShanghai 200443China Department of Prevention and Health Care Community Health Service Center of Songnan TownShanghai 200434China Department of General Practice Community Health Service Center of Songnan TownShanghai 200434China Department of Administrative Community Health Service Center of Songnan TownShanghai 200434China

BACKGROUND Type 2 diabetes mellitus(T2DM)is a leading risk factor for the development and progression of chronic kidney disease(CKD).However,an accurate and con-venient marker for early detection and appropriate management of CKD in in-dividuals with T2DM is limited.Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio(NLR)and CKD.None-theless,the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied.This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center.The total number of neutrophils and lym-phocytes was detected,and NLR levels were calculated.CKD was defined as an estimated glomerular filtration rate≤60 mL/min/1.73 m².Participants were di-vided into four groups based on NLR levels.The clinical data and biochemical characteristics were compared among groups.A multivariate logistic regression model was used to analyze the association between NLR levels and CKD.RESULTS Significant differences were found in terms of sex,serum creatinine,blood urea nitrogen,total cholesterol,and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups(P<0.0007).T2DM patients in the highest NLR quartile had a higher prevalence of CKD(P for trend=0.0011).Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters(P=0.0001,odds ratio=1.41,95%confidence intervals:1.18-1.68).CONCLUSION An elevated NLR in patients with T2DM is associated with higher prevalence of CKD,suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

关键词： Type 2 diabetes mellitus Neutrophil-to-lymphocyte ratio Chronic kidney disease Logistic regression Diabetes mellitus

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Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients

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World Journal of Gastroenterology 2024年第4期30卷 308-317页

作者： Hai-Bin Zhu Bo zhao xiao-Ting Li xiao-Yan Zhang Qian Yao Ying-Shi Sun Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of RadiologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND About 10%-31% of colorectal liver metastases(CRLM)patients would concomitantly show hepatic lymph node metastases(LNM),which was considered as sign of poor biological behavior and a relative contraindication for liver resection.Up to now,there’s still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM,except for pathology examination of lymph node after resection.AIM To compare the ability of mono-exponential,bi-exponential,and stretchedexponential diffusion-weighted imaging(DWI)models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery.METHODS In this retrospective study,97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging,including DWI with ten b values before and after chemotherapy.Various parameters,such as the apparent diffusion coefficient from the mono-exponential model,and the true diffusion coefficient,the pseudo-diffusion coefficient,and the perfusion fraction derived from the intravoxel incoherent motion model,along with distributed diffusion coefficient(DDC)andαfrom the stretched-exponential model(SEM),were measured.The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups.A nomogram was constructed to predict the hepatic lymph node status.The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient.RESULTS Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes.A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients,with an area under the curve of 0.873.Furthermore,parameters from SEM showed substantial repeatability.CONCLUSION The dev

关键词： Colorectal cancer Individualized treatment Diffusion magnetic resonance imaging Intravoxel incoherent motion Liver

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Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

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Biomedical and Environmental Sciences 2024年第1期37卷 71-84页

作者： yang Le Mei ZHENG Qi LIU xiao Jia LI Xian Xian Veronica Lim CHEN Qi zhao Zhong Hua WANG Shu yang Department of Pathology School of Basic MedicineFudan UniversityShanghai 200032China Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9054New Zealand Department of Pathology Huashan HospitalFudan UniversityShanghai 200040China Shanghai Cancer Institute Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Teladoc Health Inc Shanghai 200335China Shanghai Medical College Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Shanghai 200032China

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

关键词： miR-224-5p Exosome ULK2 p53 Cell proliferation Colorectal cancer

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Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence

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Journal of Integrative Medicine 2024年第3期22卷 258-269页

作者： Chao yang Shan-ze Wang Sheng Chen Shuo Du Guan-qun Wang Wei Guo xiao-long Xie Bi-hui Peng Shi-hao Du Ji-ping zhao Department of Acupuncture and Moxibustion Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Department of Acupuncture and Moxibustion Guangdong provincial hospital of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of MedicineShanghai 200011China Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing 100700China

Urinary incontinence (UI) is a common problem worldwide.It has a major impact on physical and social activities and interpersonal relationships.UI is common in women,but is under-reported and undertreated.It affects the quality of life of female patients severely.Acupuncture and moxibustion have been proposed as potentially effective interventions for female UI.Hence,for the benefit of acupuncture practitioners around the world,the World Federation of Acupuncture-moxibustion Societies initiated a project to develop a clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI.This CPG was developed according to the Grading of Recommendations Assessment,Development,and Evaluation (GRADE) methodology,referring to the principles of the World Health Organization Handbook for Guideline Development.During the development of the CPG,the guideline development group (GDG) played an important role.The clinical questions,recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method.This CPG contains ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions,which include nine conditional recommendations for the intervention and one conditional recommendation for either the intervention or the comparison.This CPG also provides one protocol for conventional filiform needle therapy,two therapy protocols for deep needling stimulation on lumbosacral acupoints,and four moxibustion therapy protocols,based on the protocols presented in randomized controlled trials reviewed by the GDG.

关键词： Acupuncture Clinical practice guideline Female urinary incontinence Moxibustion GRADE

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Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic

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Asian Journal of Andrology 2024年第1期26卷 41-45页

作者： Shun Bai Ming-Zhen Li yang-yang Wan Xue-Chun Hu Yi-Xun Liu Xian-Hong Tong Tong-Hang Guo Lu Zong Ran Liu Yuan-Qi zhao Ping Xiang Bo Xu xiao-Hua Jiang Department of Gynecology and Obstetrics Reproductive and Genetic HospitalThe First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China NHC Key Laboratory of Male Reproduction and Genetics Guangdong Provincial Reproductive Science Institute(Guangdong Provincial Fertility Hospital)Guangzhou 510600China Department of Urology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Wannan Medical College Wuhu 241002China

Genetic risk factors have been shown to contribute to the development of sexual dysfunction.However,the role of methylenetetrahydrofolate reductase(MTHFR)gene variants in the risk of erectile dysfunction(ED)remains unclear.In this study,we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5.The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction(PCR).No significant difference in the genotypic frequency of the MTHFR C677T polymorphism(CC,CT,and TT)was observed between men from the ED and non-ED groups.In addition,on binary logistic regression analysis,both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism.Interestingly,a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED(P=O.02).The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis,even after adjusting for potential confounders(odds ratio[OR]=2.46,95%confidence interval[CI]:1.15-5.50,P=0.02).These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED.Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routineclinicaldiagnosis.

关键词： erectile dysfunction gene variant genetic risk factors methylenetetrahydrofolate reductase sexual function

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Clinical practice guideline for acupuncture and moxibustion:Allergic rhinitis

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Journal of Integrative Medicine 2024年第3期22卷 245-257页

作者： Shi-hao Du Sheng Chen Shan-ze Wang Guan-qun Wang Shuo Du Wei Guo xiao-long Xie Bi-hui Peng Chao yang Ji-ping zhao Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing 100700China Department of Acupuncture and Moxibustion Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Department of Acupuncture and Moxibustion Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Department of Traditional Chinese Medicine Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Acupuncture is one of the most effective complementary therapies for allergic rhinitis(AR)and has been recommended by several clinical practice guidelines(CPGs)for AR.However,these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols,therefore limiting the applicability of acupuncture therapies for AR.Hence,for the benefit of acupuncture practitioners around the world,the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR.This CPG was developed according to the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)methodology,referring to the principles of the World Health Organization Handbook for Guideline Development.During the development of the CPG,the guideline development group(GDG)played an important role.The clinical questions,recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method.The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions.These include one strong recommendation for the intervention based on high-quality evidence,three conditional recommendations for either the intervention or standard care,and 11 conditional recommendations for the intervention based on very low quality of evidence.The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG.

关键词： Clinical practice guideline Allergic rhinitis Acupuncture Moxibustion GRADE

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Winter extreme precipitation over the Tibetan Plateau influenced by Arctic sea ice on interdecadal timescale

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Advances in Climate Change Research 2024年第1期15卷 42-51页

作者： Qing-Quan LI Miao BI Song yang Qing-Yuan WU Yi-Hui DING Xin-Yong SHEN xiao-Ting SUN Meng-Chu zhao China Meteorological Administration Key Laboratory for Climate Prediction Studies National Climate CentreBeijing 100081China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science and TechnologyNanjing 210044China CMA Key Open Laboratory of Transforming Climate Resources to Economy Chongqing Institute of Meteorological SciencesChongqing 401147China School of Atmospheric Sciences and Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies Sun Yat-sen University Zhuhai 519082China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519082China

The Tibetan Plateau(TP)and the Arctic are the most sensitive regions to global climate change.However,the interdecadal varibility of winter extreme precipitation over the TP and its linkage with Arctic sea ice are still unclear.In this study,the characteristics and mechisnems of the TP extreme precipitation(TPEP)influenced by Arctic sea ice on interdecadal timescale are studied based on the daily precipitation,monthly sea ice concentration and ERA5 reanalysis data from 1980 to 2018.We found that the dominant mode of the TPEP in winter mostly exhibits a uniform spatial variation on the interdecadal timescale,with an opposite weak variation in the southeastern TP,and the Arctic sea ice concentration(SIC)before 2002 are larger than that after 2003.The interdecadal variation of TPEP is affected by two teleconnection wave trains regulated by the Barents and Kara Sea ice.In the light ice years,a remarkable positive geopotential height(HGT)anomaly appears over the Barents-Kara Sea and a remarkable negative HGT anomaly is located over the Lake Baikal.Two wave trains originating over the Barents-Kara Sea can be observed.The southern branch forms a wave train through the North Atlantic along the subtropical westerly jet stream,showing a‘+-+-+'pattern of HGT anomalies from Arctic to the TP.Negative HGT anomaly controls the western TP,which creates dynamic and water vapor conditions for the TPEP.The northern branch forms a wave train through the Lake Baikal and the southeast of the TP,showing a‘+-+'HGT anomaly distribution.Positive HGT anomaly controls the southeastern TP,which is not conducive to precipitation in the region.When the SIC in the Barents-Kara Sea increases,the situation is opposite.The above analysis also reveals the reason for the difference in the east-west distribution of the TPEP.

关键词： Arctic sea ice Tibetan Plateau Winter extreme precipitation Rossby wave activity Interdecadal variation

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